Patient comfort during flexible and rigid cystourethroscopy.

INTRODUCTION: Cystourethroscopy (CS) is an endoscopic method used to visualize the urethra and the bladder. AIM: In this study, we prospectively evaluated pain in men undergoing cyclic cystoscopic assessment with rigid and flexible instruments after transurethral resection of bladder tumor (TURB). MATERIAL AND METHODS: One hundred and twenty male patients who were under surveillance after a TURB procedure due to urothelial cell carcinoma and who had undergone at least one rigid cystourethroscopy in the past were enrolled in the trial. Patients were prospectively randomized to age-matched groups for flexible (group F) or rigid (group R) CS. Patient's comfort was evaluated on an 11-grade scale, ranging from 0 (free from pain) to 10 points (unbearable pain). RESULTS: The patients described the pain during the previous rigid CS as ranging from 4 to 10 (mean: 6.8) in group F and from 0 to 10 (mean: 5.8) in group R. Group R patients described the pain during the current rigid CS as ranging from 0 to 10 (mean: 5.7). No mean change in the grade was observed between the two pain descriptions (no change 11 patients, weaker pain 25 patients, stronger pain 24 patients, gamma 0.51, p < 0.0001). Group F described the pain as 1 to 5 (mean: 2.1). In the case of flexible CS the pain experience was greatly lowered compared to the previous rigid CS. All flexible CS patients reported lowered pain (by 1 to 9 grades). Patients' age did not influence the comfort of the flexible CS or the change in pain level. CONCLUSIONS: Flexible CS is better tolerated than rigid cystoscopy by male patients regardless of patients' age.

Signaling defects in iPSC-derived fragile X premutation neurons.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a leading monogenic neurodegenerative disorder affecting premutation carriers of the fragile X (FMR1) gene. To investigate the underlying cellular neuropathology, we produced induced pluripotent stem cell-derived neurons from isogenic subclones of primary fibroblasts of a female premutation carrier, with each subclone bearing exclusively either the normal or the expanded (premutation) form of the FMR1 gene as the active allele. We show that neurons harboring the stably-active, expanded allele (EX-Xa) have reduced postsynaptic density protein 95 protein expression, reduced synaptic puncta density and reduced neurite length. Importantly, such neurons are also functionally abnormal, with calcium transients of higher amplitude and increased frequency than for neurons harboring the normal-active allele. Moreover, a sustained calcium elevation was found in the EX-Xa neurons after glutamate application. By excluding the individual genetic background variation, we have demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g. autism) and neurodegenerative (e.g. Parkinsonism, dementias) disorders.